Combined transcriptome and proteome profiling of SRC kinase activity in healthy and E527K defective megakaryocytes

Abstract

Not available.

The Analysis of the Human Megakaryocyte and Platelet Coding Transcriptome in Healthy and Diseased Subjects

“…They found that MKs differentially express mRNAs for MMPs and TIMPs, and only a subset of these are transferred to platelets. Human iPSC-derived MKs [ 62 ], CD34+ HSC-derived MKs [ 63 ] and imMKCL [ 64 , 65 ] have all been used for bulk RNA-seq studies, while similar studies have not yet been performed for primary MKs because of their low yield and the difficulty extracting them from the bone marrow. A comparison between the different types of in vitro MKs using RNA-seq datasets has not been reported.…”

“…Significant minor intron retention was detected in the patient transcriptomes for 354 MK genes, including many linked to the thrombocytopenia phenotype of platelets. Lentiviral-transduced CD34+ HSCs were generated for wild-type SRC and E527K-SRC and differentiated into MKs before applying bulk RNA-seq [ 63 ]. The E527K SRC variant causes thrombocytopenia, and MK transcriptomes for this variant showed 852 significant differentially expressed genes, with interferon I signaling as the most interesting pathway after confirmation with MK proteomics.…”

“…It was also hypothesized that a combination of platelet RNA-seq and WGS data would be of use to identify which variants in regulatory elements could be causal for an IPD [ 117 ]. Combining platelet RNA-seq and WGS data from individuals has led to important new discoveries in the study of platelet disorders [ 57 , 63 , 105 , 106 , 107 , 108 ], but its application in rare disease bioinformatics, as mentioned above, promises important novel discoveries in rare types of IPDs. Changes in gene expression and aberrant splicing events detected in the platelet transcriptome can be explained by variants in both coding and non-coding parts of the genome ( Figure 2 A,B).…”